Impact of the Conformational Variability of Oligopeptides on the Computational Prediction of their CD Spectra.
Impact of the Conformational Variability of Oligopeptides on the Computational Prediction of their CD Spectra.
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寡肽构象变异对其圆二色光谱计算预测的影响
DOI：
10.1021/acs.jpcb.9b03932
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
L. Colombi Ciacchi
中科院分区：
文献类型：
--
作者：
M. Michaelis;N. Hildebrand;R.H. Meißner;N. Wurzler;J. D. Hirst;A. Micsonai;J. Kardos;M. Delle Piane;L. Colombi Ciacchi
虽然在有序生物分子的结构测定中取得了成功，但溶液中寡肽的光谱研究受到其复杂且快速变化的构象系综的阻碍。所测量的寡肽的圆二色性（CD）光谱是所有微观状态的系综平均，严重限制了其解释，与有序的生物分子相反。光谱去卷积方法估计的二级结构的贡献，在合奏仍然主要是基于数据库的较大的有序蛋白质。在这里，我们建立了如何解释CD光谱的寡肽可以提高计算相同的观察从一组原子坐标的能力。聚焦于两个具有代表性的寡肽，分别具有已知的α-螺旋和β-发夹基序的倾向，我们比较和交叉验证来自实验CD光谱的去卷积，基于序列的从头结构预测和基于增强采样方法的分子动力学模拟的结构信息。我们发现，小的构象变化可以引起CD信号的显着变化。虽然对于α-螺旋肽从头结构预测的更简单构象景观已经可以给出与实验的合理一致性，但对于β-发夹序列，需要考虑构象异构体的扩展系综。
Although successful in the structural determination of ordered biomolecules, the spectroscopic investigation of oligopeptides in solution is hindered by their complex and rapidly changing conformational ensemble. The measured circular dichroism (CD) spectrum of an oligopeptide is an ensemble average over all microstates, severely limiting its interpretation, in contrast to ordered biomolecules. Spectral deconvolution methods to estimate the secondary structure contributions in the ensemble are still mostly based on databases of larger ordered proteins. Here, we establish how the interpretation of CD spectra of oligopeptides can be enhanced by the ability to compute the same observable from a set of atomic coordinates. Focusing on two representative oligopeptides featuring a known propensity toward an α-helical and β-hairpin motif, respectively, we compare and cross-validate the structural information coming from deconvolution of the experimental CD spectra, sequence-based de novo structure prediction, and molecular dynamics simulations based on enhanced sampling methods. We find that small conformational variations can give rise to significant changes in the CD signals. While for the simpler conformational landscape of the α-helical peptide de novo structure prediction can already give reasonable agreement with the experiment, an extended ensemble of conformers needs to be considered for the β-hairpin sequence.
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影响因子：
3.9
作者：
Burkett, SL;Read, MJ
通讯作者：
Read, MJ
二氧化硅-肽界面的相互作用：功能化程度对构象整体的影响。
DOI：
10.1021/acs.langmuir.8b00874
发表时间：
2018
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Anna Sola;Monika Michaelis;Daniel J. Oliver;M. Roe;L. Colombi Ciacchi;H. Heinz;C. Perry
通讯作者：
C. Perry
影响因子：
3
作者：
Duan, Y;Wu, C;Kollman, P
通讯作者：
Kollman, P
区分 GB1 肽的结构整体：REMD 模拟和 NMR 实验。
影响因子：
15
作者：
Weinstock,DanielS;Narayanan,Chitra;Felts,AnthonyK;Andrec,Michael;Levy,RonaldM;Wu,Kuen-Phon;Baum,Jean
通讯作者：
Baum,Jean
影响因子：
3
作者：
Bernardi, Rafael C.;Melo, Marcelo C. R.;Schulten, Klaus
通讯作者：
Schulten, Klaus